help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shimojo, M.
Right arrow Articles by Stewart, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shimojo, M.
Right arrow Articles by Stewart, P. M.
Endocrinology Vol. 138, No. 3 1305-1311
Copyright © 1997 by The Endocrine Society

Articles

Immunodetection of 11ß-Hydroxysteroid Dehydrogenase Type 2 in Human Mineralocorticoid Target Tissues: Evidence for Nuclear Localization1

Masako Shimojo, Marie L. Ricketts, Massimiliano D. Petrelli, Phillip Moradi, Gerald D. Johnson, A. R. Bradwell, Martin Hewison, Alexander J. Howie and Paul M. Stewart2

Departments of Medicine, Immunology (G.D.J., A.R.B.) and Pathology (A.J.H.), University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom B15 2TH

Address all correspondence and requests for reprints to: Prof. Paul M. Stewart, Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom B15 2TH.

11ß-Hydroxysteroid dehydrogenase (11ßHSD) is an enzyme complex responsible for the conversion of hormonally active cortisol to inactive cortisone; two isoforms of the enzyme have been cloned and characterized. Clinical observations from patients with the hypertensive syndrome apparent mineralocorticoid excess, recently explained on the basis of mutations in the human 11ßHSD2 gene, suggest that it is the 11ßHSD2 isoform that serves a vital role in dictating specificity upon the mineralocorticoid receptor (MR). We have raised a novel antibody in sheep against human 11ßHSD2 using synthetic multiantigenic peptides and have examined the localization and subcellular distribution of 11ßHSD2 in mineralocorticoid target tissues.

The immunopurified antibody recognized a single band of approximately 44 kDa in placenta, trophoblast, and distal colon. In kidney tissue, two bands of approximately 44 and 48 kDa were consistently observed. No signal was seen in decidua, adrenal, or liver. Immunoperoxidase studies on the mineralocorticoid target tissues, kidney, colon, and parotid gland indicated positive staining in epithelial cells known to express the MR: respectively, renal collecting ducts, surface and crypt colonic epithelial cells, and parotid duct epithelial cells. No staining was seen in these tissues in other sites. The intracellular localization of 11ßHSD2 in kidney and colon epithelial cells was addressed using confocal laser microscopy. Parallel measurements of 11ßHSD2 and nuclear propidium iodide fluorescence on sections scanned through an optical section of approximately 0.1 µm indicated significant 11ßHSD2 immunofluorescence in the nucleus.

In human kidney, colon, and salivary gland, 11ßHSD2 protects the MR from glucocorticoid excess in an autocrine fashion. Furthermore, within these tissues, 11ßHSD2, which had been considered to be a microsomal enzyme, is also found in the nucleus, suggesting that the interaction between the MR and aldosterone or cortisol is in part a nuclear event.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
J. Kim, K. A. Temple, S. A. Jones, K. N. Meredith, J. L. Basko, and M. J. Brady
Differential Modulation of 3T3-L1 Adipogenesis Mediated by 11beta-Hydroxysteroid Dehydrogenase-1 Levels
J. Biol. Chem., April 13, 2007; 282(15): 11038 - 11046.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
C. U Onyimba, N. Vijapurapu, S J. Curnow, P. Khosla, P. M Stewart, P. I Murray, E. A Walker, and S. Rauz
Characterisation of the prereceptor regulation of glucocorticoids in the anterior segment of the rabbit eye.
J. Endocrinol., August 1, 2006; 190(2): 483 - 493.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
M. Quinkler, D. Zehnder, J. Lepenies, M. D Petrelli, J. S Moore, S. V Hughes, P. Cockwell, M. Hewison, and P. M Stewart
Expression of renal 11{beta}-hydroxysteroid dehydrogenase type 2 is decreased in patients with impaired renal function
Eur. J. Endocrinol., August 1, 2005; 153(2): 291 - 299.
[Abstract] [Full Text] [PDF]

Home page
 Reproductive SciencesHome page
H. Chisaka, J. F. Johnstone, M. Premyslova, Z. Manduch, and J. R.G. Challis
Effect of Pro-inflammatory Cytokines on Expression and Activity of 11{beta}-Hydroxysteroid Dehydrogenase Type 2 in Cultured Human Term Placental Trophoblast and Human Choriocarcinoma JEG-3 Cells
Reproductive Sciences, July 1, 2005; 12(5): 303 - 309.
[Abstract] [PDF]

Home page
 Physiol. Rev.Home page
C. A. Wagner, K. E. Finberg, S. Breton, V. Marshansky, D. Brown, and J. P. Geibel
Renal Vacuolar H+-ATPase
Physiol Rev, October 1, 2004; 84(4): 1263 - 1314.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
R. Norregaard, T. R. Uhrenholt, C. Bistrup, O. Skott, and B. L. Jensen
Stimulation of 11-{beta}-hydroxysteroid dehydrogenase type 2 in rat colon but not in kidney by low dietary NaCl intake
Am J Physiol Renal Physiol, August 1, 2003; 285(2): F348 - F358.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
N. Alfaidy, S. Gupta, C. DeMarco, I. Caniggia, and J. R. G. Challis
Oxygen Regulation of Placental 11{beta}-Hydroxysteroid Dehydrogenase 2: Physiological and Pathological Implications
J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4797 - 4805.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Kataoka, A. Kudo, H. Hirano, H. Kawakami, T. Kawano, E. Higashihara, H. Tanaka, F. Delarue, J.-D. Sraer, T. Mune, et al.
11{beta}-Hydroxysteroid Dehydrogenase Type 2 Is Expressed in the Human Kidney Glomerulus
J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 877 - 882.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. Y. H. Zhang, X. Wang, J. T. Wang, N. A. Compagnone, S. H. Mellon, J. L. Olson, H. S. Tenenhouse, W. L. Miller, and A. A. Portale
Dietary Phosphorus Transcriptionally Regulates 25-Hydroxyvitamin D-1{alpha}-Hydroxylase Gene Expression in the Proximal Renal Tubule
Endocrinology, February 1, 2002; 143(2): 587 - 595.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
S. Rauz, E. A. Walker, C. H. L. Shackleton, M. Hewison, P. I. Murray, and P. M. Stewart
Expression and Putative Role of 11{beta}-Hydroxysteroid Dehydrogenase Isozymes within the Human Eye
Invest. Ophthalmol. Vis. Sci., August 1, 2001; 42(9): 2037 - 2042.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Korbonits, I. Bujalska, M. Shimojo, J. Nobes, S. Jordan, A. B. Grossman, and P. M. Stewart
Expression of 11{beta}-Hydroxysteroid Dehydrogenase Isoenzymes in the Human Pituitary: Induction of the Type 2 Enzyme in Corticotropinomas and Other Pituitary Tumors
J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2728 - 2733.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
P.M. Driver, M.D. Kilby, I. Bujalska, E.A. Walker, M. Hewison, and P.M. Stewart
Expression of 11{beta}-hydroxysteroid dehydrogenase isozymes and corticosteroid hormone receptors in primary cultures of human trophoblast and placental bed biopsies
Mol. Hum. Reprod., April 1, 2001; 7(4): 357 - 363.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
G. J. Pepe, M. G. Burch, and E. D. Albrecht
Localization and Developmental Regulation of 11{beta}-Hydroxysteroid Dehydrogenase-1 and -2 in the Baboon Syncytiotrophoblast
Endocrinology, January 1, 2001; 142(1): 68 - 80.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
D. ZEHNDER, R. BLAND, E. A. WALKER, A. R. BRADWELL, A. J. HOWIE, M. HEWISON, and P. M. STEWART
Expression of 25-Hydroxyvitamin D3-1{alpha}-Hydroxylase in the Human Kidney
J. Am. Soc. Nephrol., December 1, 1999; 10(12): 2465 - 2473.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
A. Odermatt, P. Arnold, A. Stauffer, B. M. Frey, and F. J. Frey
The N-terminal Anchor Sequences of 11beta -Hydroxysteroid Dehydrogenases Determine Their Orientation in the Endoplasmic Reticulum Membrane
J. Biol. Chem., October 1, 1999; 274(40): 28762 - 28770.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
M. Tetsuka, M. Milne, G.E. Simpson, and S.G. Hillier
Expression of 11ß-Hydroxysteroid Dehydrogenase, Glucocorticoid Receptor, and Mineralocorticoid Receptor Genes in Rat Ovary
Biol Reprod, February 1, 1999; 60(2): 330 - 335.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. Condon, C. Gosden, D. Gardener, P. Nickson, M. Hewison, A. J. Howie, and P. M. Stewart
Expression of Type 2 11{beta}-Hydroxysteroid Dehydrogenase and Corticosteroid Hormone Receptors in Early Human Fetal Life
J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4490 - 4497.
[Abstract] [Full Text]

Home page
 FASEB J.Home page
G. Mazzocchi, G. P. Rossi, G. Neri, L. K. Malendowicz, G. Albertin, and G. G. Nussdorfer
11ß-Hydroxysteroid dehydrogenase expression and activity in the human adrenal cortex
FASEB J, November 1, 1998; 12(14): 1533 - 1539.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
K. E. Sheppard, K. Khoo, Z. S. Krozowski, and K. X. Z. Li
Steroid specificity of the putative DHB receptor: evidence that the receptor is not 11beta HSD
Am J Physiol Endocrinol Metab, July 1, 1998; 275(1): E124 - E131.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Naray-Fejes-Toth and G. Fejes-Toth
Extranuclear Localization of Endogenous 11{beta}-Hydroxysteroid Dehydrogenase-2 in Aldosterone Target Cells
Endocrinology, June 1, 1998; 139(6): 2955 - 2959.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. L. Ricketts, J. M. Verhaeg, I. Bujalska, A. J. Howie, W. E. Rainey, and P. M. Stewart
Immunohistochemical Localization of Type 1 11{beta}-Hydroxysteroid Dehydrogenase in Human Tissues
J. Clin. Endocrinol. Metab., April 1, 1998; 83(4): 1325 - 1335.
[Abstract] [Full Text]

Home page
 Cardiovasc ResHome page
S. H.M. van Uum, A. R.M.M. Hermus, P. Smits, T. Thien, and J. W.M. Lenders
The role of 11{beta}-hydroxysteroid dehydrogenase in the pathogenesis of hypertension
Cardiovasc Res, April 1, 1998; 38(1): 16 - 24.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. E. Smith, L. A. Salamonsen, P. A. Komesaroff, K. X. Z. Li, K. M. Myles, M. Lawrence, and Z. Krozowski
11{beta}-Hydroxysteroid Dehydrogenase Type II in the Human Endometrium: Localization and Activity during the Menstrual Cycle
J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 4252 - 4257.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
G. Hirasawa, H. Sasano, K.-i. Takahashi, K. Fukushima, T. Suzuki, N. Hiwatashi, T. Toyota, Z. S. Krozowski, and H. Nagura
Colocalization of 11{beta}-Hydroxysteroid Dehydrogenase Type II and Mineralocorticoid Receptor in Human Epithelia
J. Clin. Endocrinol. Metab., November 1, 1997; 82(11): 3859 - 3863.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1997 by The Endocrine Society